Abstract Current treatment guidelines recommend maintenance of HIV-1 viral load below detectable levels (<50 copies per milliliter), even in extensively treated patients with multidrug-resistant HIV-1. Given recent advances in drug development and the availability of new agents with activity against antiretroviral-resistant HIV-1 viral strains, this goal is increasingly attainable for treatment-experienced patients. A stepwise approach to management of patients harboring antiretroviral-resistant HIV is presented, including assessment of adherence, a description of the use of resistance testing and utilization of new antiretroviral agents.